Despite advances in treatment, epithelial ovarian cancer remains the fourth leading cause of cancer death in American women. This program, now in its 12th year, has focused on the immunology and management of epithelial ovarian cancer. In the last funding period, the program was responsible for the cloning of the MUC16/CA125 antigen, the development of a series of monovalent cancer vaccines directed at ovarian cancer epitopes and a number of studies related to consolidation therapy of patients in complete remission. Clinical trials of combination therapy in the primary treatment setting and for recurrent disease were also completed. Goals for the next period will be 1. To examine the molecular genetics of MUC16 / Muc16 in the pathophysiology of ovarian cancer and develop the scientific basis for possible MUC16 based treatment opportunities; 2. To develop both humoral and cellular strategies for ovarian cancer treatment to be used in the minimal residual disease setting, emphasizing MUC16 as a target; 3. To clinically test immunological and other non-cytotoxic therapies in consolidation therapy in Phase I pilot studies and in carefully designed definitive Phase II studies with appropriate correlative studies; and 4. To develop and test platinum based combinations with novel agents in re-induction. Each of the 4 projects in this competing renewal is directed at one or these goals. In a continuing project, we extend our studies of MUC16/CA125 into the genetic structure of MUC16 and the role expression of MUC16 has in the malignant phenotype. A second continuing project completes our examination of synthetic carbohydrate/peptide vaccines and initiates a new strategy for the development of T-cell vaccines, based in part on the MUC16 sequence. A new project will investigate the in vitro amplification of tumor antigen specific cytotoxic T cells for adoptive therapy, employing HLA restricted epitopes from WT1 and MUC16. In the last continuing project, a clinical program will focus on re-induction of second remission with novel platinum based combinations and consolidation therapy for patients with minimal residual disease. Models of CA125 behavior are also explored in this project. Three themes unite these projects including the structure of MUC16/CA125 antigen and its biology; consolidation therapy as a novel strategy in ovarian cancer and a a commitment for the development of immunologic therapies for ovarian cancer.